Background: Amidst escalating global challenges such as antimicrobial resistance and post-COVID therapeutic gaps, dihydropyrimidines (DHPs) and their thione derivatives have emerged as a highly promising scaffold for drug development. This systematic review aims to consolidate recent advancements (2020–2025) and evaluate the synthetic innovation, structure–activity relationships (SAR), and preclinical potential of these compounds. Methods: A systematic review was conducted according to PRISMA guidelines, searching multiple electronic databases (Scopus, PubMed, Web of Science). Sixty original studies from 2020 to 2025 meeting predefined inclusion criteria were selected for data extraction and qualitative synthesis. Results: The analysis reveals a surge in publications (over 300% since 2020). Key structural modifications, such as N-methylation to improve bioavailability and specific substitutions at C4/C5 positions, significantly enhance biological potency, yielding strong inhibitory effects against viral proteases and cancer cell lines. Notable compounds include the apoptosis inducer LaSOM 65 and multitarget Ru(II)–Biginelli hybrids. Conclusions: This review affirms the timeliness and translational potential of the DHP scaffold. The field shows bright prospects for advancing to phase I trials by 2030, urging intensified exploration to unlock novel pharmaceuticals from this versatile chemotype.

Background/Objectives: The development of multifunctional biomaterials for bone regeneration remains a key challenge in additive manufacturing. Although polylactic acid (PLA) is widely used in fused deposition modeling (FDM), its limited bioactivity and lack of intrinsic antibacterial functionality restrict its application in implantable constructs. This study aimed to develop a PLA-based composite filament combining ion-mediated bioactive potential and local antibacterial functionality using a Quality by Design (QbD) approach. Methods: PLA-based composite filaments incorporating a mollusk shell-derived biogenic calcium-containing filler (20 wt.%) and gentamicin (5 wt.%) were fabricated by solvent-free melt extrusion. A QbD framework was applied to define the Quality Target Product Profile (QTPP), identify critical quality attributes (CQAs), and assess critical material attributes (CMAs) and critical process parameters (CPPs). The material was characterized by SEM–EDS combined with ImageJ-based quantitative image analysis, TGA/DSC, mechanical testing, ICP-AES analysis of aqueous extracts, agar diffusion antibacterial assays, FDM printability assessment, and in vivo biocompatibility testing in a rat subcutaneous implantation model. Results: The developed PLA–Gen–MS material was obtained as a continuous filament with a diameter of 1.75 ± 0.05 mm and was successfully used for FDM printing of model scaffold structures. SEM–EDS confirmed matrix continuity and distribution of the calcium-containing mineral phase. ICP-AES revealed a calcium-dominant multicomponent ion release profile, with Ca as the predominant element and measurable levels of Sr, Mg, P, Mn, and Fe. TGA/DSC confirmed thermal compatibility of the components under melt-processing conditions. PLA–Gen–MS demonstrated antibacterial activity against all tested strains, with inhibition zones of approximately 20–21 mm. In vivo, the material showed a favorable preliminary tissue response compared with TiLOOP^®, including faster reduction of inflammatory infiltration and absence of foreign body giant cells by day 14. Conclusions: The QbD-guided strategy enabled the development of a multifunctional PLA-based filament integrating melt processability, structural integrity, ion-mediated bioactive potential, antibacterial functionality, printability, and favorable preliminary biocompatibility. PLA–Gen–MS can be considered a promising platform for further development of personalized bioactive and antibacterial scaffold constructs for bone regeneration.

Background: Topical semi-solid dosage forms are crucial for treating inflammatory skin disorders, wounds, burns, and superficial infections. Despite their widespread clinical use, comprehensive pharmaceutical market analyses of registered topical medicines remain limited in Central Asia. The aim of this study was to characterize the pharmaceutical market of topical semi-solid dosage forms registered in the Republic of Kazakhstan, including their dosage-form distribution, pharmacotherapeutic composition, manufacturer structure, and structural diversity of active pharmaceutical ingredients (APIs), with particular attention to heterocyclic compounds. Methods: A cross-sectional descriptive analysis was conducted using the State Register of Medicinal Products of the Republic of Kazakhstan. Registration records of topical semi-solid dosage forms were identified according to predefined inclusion criteria and classified by dosage form, pharmacotherapeutic category, manufacturer, country of origin, and API chemical structure. Descriptive statistical analysis, market concentration indices, and structural classification of heterocyclic compounds were applied. Therapeutic recommendations for dermatitis management from selected CIS countries were reviewed to provide a contextual interpretation of the observed market structure. Results: A total of 1046 registered topical semi-solid dosage forms met the inclusion criteria. Ointments (39.5%), gels (28.9%), and creams (25.4%) accounted for 93.8% of all registered products, indicating a highly concentrated dosage-form structure. Anti-inflammatory agents represented the largest pharmacotherapeutic group, whereas wound-healing and combination products accounted for smaller proportions of the market. Structural classification demonstrated broad representation of established heterocyclic chemical classes, while no registered medicinal products containing dihydropyrimidine-2(1H)-thione (DHPM-thione) derivatives were identified in the registry. Comparison with regional clinical recommendations indicated differences between recommended therapeutic approaches and the distribution of registered pharmacotherapeutic categories. Conclusions: This study provides the first comprehensive descriptive assessment of the registered market of topical semi-solid dosage forms in Kazakhstan. The results establish a reference dataset describing the current pharmaceutical landscape, including dosage forms, therapeutic categories, manufacturers, and API chemical classes. The absence of registered DHPM-thione-containing medicinal products indicates that this chemical class is currently not represented in the national medicines registry. Together with previously published preclinical evidence, this observation supports consideration of DHPM-thione derivatives as a subject for future pharmaceutical research, although the present study does not permit conclusions regarding their clinical effectiveness, market demand, or future commercialization.